Implication of UNconventionaL T Lymphocytes in Cystic Fibrosis (UNLOCk)

NCT03886350 | Completed

• 2 other identifiers: RIPH3-RNI18 / UNLOCk2019-A00290-57
• Study Type: observational
• Target: 62
• Locations: 1 country
• Sites: 2

Brief Summary

Cystic fibrosis (CF) is characterized by a decrease in mucociliary clearance, recurrent infections and airway inflammation. This inflammatory process in airway mucosa is persistent, uncontrolled, but, somewhat paradoxically, ineffective for pathogen clearance. Neutrophils are chronically recruited in the airway mucosa by proinflammatory mediators such as Interleukin (IL)-17. However, mechanisms involved in this dysregulated and persistent immune response are not well understood. In this context, a heterogeneous subpopulation of T lymphocytes called "unconventional T cells" (UTC) should deserve greater attention. UTC play a key role in orchestrating the ensuing innate and adaptive immune responses and they are endowed with numerous regulatory and effector properties. UTC mainly establish residency at mucosal sites, including the lung. To date, however, data related to implication and behavior of UTC during cystic fibrosis are extremely limited. The hypothesis is that, given UTC properties, their functions and behavior are altered in CF, and thus, these cells could be implicated in persistent inflammation and poor response to infections. The objective is to study UTC properties and functions in cystic fibrosis using blood and sputum samples of patients with CF, in correlation with comprehensive clinical and microbiological data. The study will enroll adult patients with CF followed-up at University Hospital of Tours, France. For each patient included, blood and sputum samples will be analyzed during 18 months 1/ from routine tests obtained at steady state and 2/ from tests performed during acute exacerbations. UTC will be explored in blood and sputum using flowcytometry approach, to evaluate their relative abundance, activation/inhibition profile and functions (cytokine production and cytotoxic ability). Correlation will be made with clinical status, with longitudinal comparison across the study period for each patient, and comparison with the other patients and healthy volunteers. This study will add significant knowledge in CF immunopathology by comprehensively assess UTC presence, functions and activation in CF. Indeed, UTC could be explored for disease progression marker, and, in a long-term perspective, explored for therapeutic interventions aiming at modulating their function (by activating or inhibiting UTC), to reshape lung immune response during CF.

Conditions

Cystic Fibrosis; Innate Immunity; Inflammatory Response

Keywords

Unconventional T cells; Cystic fibrosis; gamma delta T cell; Mucosal Associated Invariant T cell; Natural Killer T cell

Outcome Measures

Primary Outcomes (2)

• Blood level of Non-Conventional T Lymphocytes

  Blood UTC expressed as % Cluster of Differenciation 3+ (CD3+) lymphocytes (gamme delta T lymphocytes, MAIT cells, Natural Killer T cells)

  18 months

• Sputum level of Non-Conventional T Lymphocytes

  Sputum UTC expressed as % CD3+ lymphocytes (gamme delta T lymphocytes, MAIT cells, Natural Killer T cells)

  18 months

Secondary Outcomes (3)

• UTC activation/inhibition profile

  18 months

• UTC production of pro-inflammatory cytokines

  18 months

• UTC capacity to mediate cytotoxicity

  18 months

Study Arms (1)

Patients with cystic fibrosis

Patients with CF whom follow-up is undertaken at University Hospital of Tours, France

Other: blood and sputum samples

Interventions

blood and sputum samples OTHER

Blood and sputum samples for research purpose collected during routine tests performed at steady state and acute exacerbation

Patients with cystic fibrosis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Adult patients with cystic fibrosis whom follow-up is undertaken at University Hospital of Tours.

You may qualify if:

• Patients with a genetic diagnosis of cystic fibrosis
• Older than 18 years old
• Be followed-up at University Hospital of Tours

You may not qualify if:

• Pregnant or breastfeeding women
• Patient under judicial protection
• Patient having objected to the processing of his data

Sponsors & Collaborators

• University Hospital, Tours: lead

Study Sites (2)

Cystic Fibrosis Resource and Competence Center, University Hospital, Tours

Tours, 37044, France

Location

Pulmonology Department, University Hospital, Tours

Tours, 37044, France

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood samples Sputum samples

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Youenn JOUAN, MD

  University Hospital, Tours

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2019
• First Posted: March 22, 2019
• Study Start: April 3, 2019
• Primary Completion: July 16, 2020
• Study Completion: July 20, 2020
• Last Updated: June 23, 2022

Record last verified: 2022-06

Locations

FR (2)